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| Primary information |
|---|
| ID | 10576 |
| Therapeutic ID | Th1117 |
| Protein Name | Ipilimumab |
| Sequence | >Th1117_Ipilimumab
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 148000 |
| Chemical Formula | C6572H10126N1734O2080S40 |
| Isoelectric Point | 6.1-8.5 |
| Hydrophobicity | NA |
| Melting point | 80-90 ºC |
| Half-life | 14.7 days |
| Description | Recombinant, human monoclonal IgG1 kappa immunoglobin. It is an antineoplastic agent developed by Bristol-Myers Squibb and Medarex for the treatment of unresectable or metastatic melanoma in adults. Ipilimumab received FDA approval on March 25, 2011. |
| Indication/Disease | Ipilimumab is indicated for the treatment of unresectable or metastatic melanoma in adults. |
| Pharmacodynamics | The pharmacodynamics of Ipilimumab are not completely understood. In melanoma patients receiving Ipilimumab, the mean peripheral blood absolute lymphocyte counts (ALC) increased throughout the induction dosing period. This increase occurred in a dose-dependent fashion in Phase 2 studies. Ipilimumab given with or without gp100 at 3 mg/kg increased ALC throughout the induction dosing period, but no meaningful change in ALC occurred in the control group who received an investigational peptide vaccine alone. Furthermore, ipilimumab binds to CTLA-4 with high affinity (Kd = 5.24 ± 3.62 nM). As a result, ligands CD80 and CD86 are blocked from binding to CTLA-4 with a minimum EC50 value of 0.2 μg/mL. |
| Mechanism of Action | Ipilimumab is a fully human IgG1K antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that is indicated for unresectable or metastatic melanoma. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells. The proposed mechanism of action is indirect, and may be through T-cell - mediated anti-tumor immune responses. |
| Toxicity | Data regarding ipilumumab overdose is not readily available.[L12126] However, the most common adverse reactions to ipilumumab are fatigue, diarrhea, pruritus, rash, and colitis.[L12126] |
| Metabolism | The metabolism of ipilimumab does not involve the cytochrome P450 enzyme system.[L12126,L12642] Because ipilimumab is a protein, it is expected to be degraded into small peptides and amino acids by proteolytic enzymes.[A35122] |
| Absorption | Cmax was 65.8µg/mL for 2-6 year olds, 70.1µg/mL for 6-<12 year olds, and 73.3µg/mL in patients 12 years and older.[L12126] Data regarding the AUC and Tmax of ipilumumab are not readily available.[A35118,L12126] |
| The volume of distribution at steady-state of ipilimumab is 7.21L.[A35118] |
| Clearance | Ipilimumab has a clearance of 15.3 mL/hr.[A35118] Systemic clearance increases proportionally with body weight.[L12642] |
| Categories | Antineoplastic Agents and Monoclonal antibodies |
| Patents Number | CA2381770 |
| Date of Issue | 8-Jul-2007 |
| Date of Expiry | 8-Aug-2020 |
| Drug Interaction | NA |
| Target | Cytotoxic T-lymphocyte protein 4 |
| Brand Name | YERVOY |
| Company | Bristol-Myers Squibb |
| Brand Description | Bristol-Myers Squibb |
| Prescribed For | YERVOY is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma |
| Chemical Name | NA |
| Formulation | It is supplied in single-use vials of 50 mg/10 mL and 200 mg/40 mL. Each milliliter contains 5 mg of ipilimumab and the following inactive ingredients: diethylene triamine pentaacetic acid (DTPA) (0.04 mg), mannitol (10 mg), polysorbate 80 (vegetable origin) (0.1 mg), sodium chloride (5.85 mg), tris hydrochloride (3.15 mg), and Water for Injection, USP at a pH of 7. |
| Physical Appearance | Sterile, preservative-free, clear to slightly opalescent, colorless to pale-yellow solution |
| Route of Administration | Intravenous |
| Recommended Dosage | The recommended dose of YERVOY is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of 4 doses. |
| Contraindication | Immune-mediated adverse reactions: Permanently discontinue for severe reactions. Less than 7.5 mg prednisone or equivalent per day is administered or systemic high-dose corticosteroids are adminstered for severe, persistent, or recurring immune-mediated reactions. |
| Side Effects | Most common adverse reactions are fatigue, diarrhea, pruritus, rash, and colitis. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |